Plasticity of the Immature Brain:Sensory Deprivation,

Focal Lesions

Shani HaglerIsabelle Rapin

Child Neurology:September 25, 2013

No conflict of interest

Brain Plasticity

The structure of the brain is a function of

the genetic programs that orchestrate its

development

and

inputs from the environment

A. Sensory deprivation

Environmental effect on development of cortical neurons in fish:

Brought upalone

Brought up with others

Cover of

Science !

Brain Plasticity

In humans and animals

damage or sensory deprivation

→

structural alteration (limited) of subcortical relays and sensory cortex

potential for (partial) functional recovery / substitution

Brain Plasticity

Lack of major sensory input

(deafness, blindness, limb amputation, etc.)

→

major reorganization of sensory cortex, with spared modalities occupying (partially) deafferented sensory areas

Variables that affect brain reorganization

Age at sensory deprivation Completeness of the sensory loss Interval since sensory loss Stimulation following the sensory loss

Unilaterally Deafened Animals: Subcortical Plasticity

More immature animals → greater effect

Sound deprivation, cochlear destruction →

structural reorganization of brainstem

nuclei, competitive innervation

Decreased number, smaller neurons

Dendritic atrophye.g., Webster, Clopton, Parks, Rubel

Human: Subcortical Plasticity

Down infant (middle ear effusion) →

♦ ventral cochlear nuclei smaller; fewer neurons

Cockayne syndrome (cochlear degeneration) →

♦ ventral cochlear nucleus, medial olive, inferior

colliculus: neurons small

♦ medial geniculate, Heschl gyrus: neurons normal !

Gandolfi, 1981, 1993

Plasticity: Differences in Early Sound Exposure in Animals →

Decrease affects sound localization and visual/auditory maps in tectum

Patterned sound exposure affects sound selectivity of collicular neurons in rats, mice

Selective cochlear lesions change tonotopic map in auditory cortex in cats

Discrimination training changes tonotopic map in auditory cortex in owls

Deafness increase visual responses in auditory cortex in cats

Plasticity: Early Speech Sound Exposure in Humans

Neonate: makes many speech sound discriminations

1 year old: loss of irrelevant, honing of relevant speech sound discriminations

Toddler/preschooler: learn new language accent-free

Older child/adult: accented new language; do not hear irrelevant contrasts (e.g. L/R)

Bilateral Congenital Vestibular Dysfunction:

Effect on Sitting and Walking (N=22)

• No nystagmus or vertigo

• May have delayed head control, hypotonia

• Age at sitting: 8 months ( 6 – 24)

• Age at walking: 16.5 months (10 – 48)

• Danger: swimming under waterRapin 1974

Brain differences in early blindness

Normally - 1/3 of cortex involved in visual processing

Blinded animal studies: new projections from inferior colliculus (auditory) to lateral geniculate nucleus (normally visual)

Anatomy: - Gray&white matter atrophy of visual networks - Increase in cortical thickness in cuneus (decreased

pruning?)

Metabolism:- 15% ↑ glucose metabolism in striate and extrastriate cortex

Kupers et al, 2011

A. Gray matter - red, white matter - blueB. Increased cortical thickness of cuneusC. Increased glucose metabolism Kupers et al. 2011

Brain imaging in congenital/early blindness

Cross-modal plasticity Occipital cortex (OC) - shift from processing visual other sensory

modalities ? explains extraordinary auditory & tactile abilities in the blind

TACTLE: - ↑ tactile acuity - Braille activates OC only in congenital/early onset blindness - TMS disrupting occipital lobe errors in Braille & paresthesias in fingers - TDU (computer game) training for one week blind activated visual

cortex AUDITORY: - 1/2 EOB: ↑ localization mono-aural sound - activates specific OC areas

SPACIAL PERCEPTION: - CB unaffected by hand crossing in determining order of hand touched

Kupers et al 2011Ptito et al 2008

Cohen et al 1999Frasnelli et al 2011

Crossmodal plasticity in early blind

OLFACTION - ↑ odor identification - odor detection → ↑ blood oxygenation level-

dependent (BOLD) responses in primary & higher order olfactory & occipital cortices

HIGHER CORTICAL FUNCTION - repetition priming (-rTMS) over to visual

cortex → slows Braille reading

Kupers et al 2011

Brain consequence of sensory deprivation

Cortical reorganization hypothesis- cross-modal brain responses = formation of new pathways in the sensory-deprived brain

vs.Unmasking hypothesis

- loss of a sensory input → unmasking and strengthening of preexisting neuronal connections

Kupers et al 2011

Plasticity in focal early lesions in visual pathway

Less clearly correlated field cuts with early than late focal lesions

Infant with perinatal stroke of L optic radiations - at 3 months: visual cortical activation only of unaffected side - at 20 months: activation of visual cortex on affected side reorganization of thalamo-cortical pathway

Early visual field defecit - less ↓ in environmental navigation - in cats: entire visual cortex removed visual orientation

unaffected due to reorganization of subcortical to extrastriatal visual pathways

Seghier et al., 2004

-LEFT--potential by-pass of lesion potential full recovery of conscious vision.

-RIGHT-- no full recovery of conscious vision. Expanded collicular -- extrastriate cortex ~ normal visual exploration & navigation

Cionni et al 2011

Damage Lt optic radiation

Damage Rt striate cortex:

Early lesions in central visual pathway in cat

Hemiplegic CP

Corticospinal Tract Development Reaches cervical cord by 24 wks

Begins myelination by 40 weeks

Newborn: both ipsi- and contralateral corticospinal innervation of spinal motor neuron pools

By 2yrs - Rapid differential development of the ipsilateral and contralateral tracts. Dominance of the contralateral (crossed) tract

In hemiplegia: ipsilateral dominance progressively detrimental competes with residual contralateral tract

JA Eyre et al., 2007

Sensorimotor Reorganization in CP*

Motor: both ipsi- and contralesional cortical reorganization

Somatosensory: predominantly ipsilesional reorganization motor + sensory lesion: interhemispheric dissociation of motor/sensory functions

Motor cortex lesion – total loss of crossed tract rare- activity-dependent competition for ipsi- vs. contralesional access

to spinal motor neuron pool (TMS & EMG)- role of somatosensory feedback from affected limb

*pattern depends on timing, size, & location of lesion.

Guzzella et al. 2007

Main types of sensorimotor reorganization in lateralized damage

Cionni et al. 2011

CP & Hand Function

Finger dexterity: correlation atrophy of thalamo-cortical > than cortico-spinal tract

Contralateral slower than ipsilateral hand Bimanual: both slow “ : contralateral better than when

unimanual

Rose et al., 2011

Steenbergen et al., 2008

Hemiparetic CP in Perspective

• Dynamic motor deficit Immature cortico-spinal hemi not present beforeof 6 mos Worsening hemi: competition of uncrossed and crossed

cortico-spinal tracts tract for spinal motor neurons Very early lesion: uncrossed tract may compensate

• Importance of sensory deficit for prognosis

• If sensory & motor reorginization in different hemispheres severity of deficits poorly coordinated

• Neglect: Lt lesion ± mild bilateral

• Rt lesion ± ↓ attention, ↓ spacial skills

Katz et al 1998

B. Focal lesions

Language areas in the left hemisphere

Language in the brain:distributed network

Language processing is bi-hemispheric:♦ Lt >> Rt: phonology, syntax, semantics

♦ Rt >> Lt: prosody, pragmatics

♦ Both (L >> R): lexicon

Lt. superior temporal: phonologic decoding Lt. inferior frontal: encoding phonology/syntax Suprasylvian temporo-parietal: lexical processing Cerebellum: encoding automaticity etc. Etc.

Language in early lateralized brain lesion

Language will develop whether lesion in the Rt or Lt hemisphere (plasticity)

Location of lesion does not predict type of language deficit !!

Language is delayed, but catches up by school age

Price to pay for plasticity: visuo-spatial deficits likely

E. Bates et al.

Early acquired aphasia vs. developmental language disorder

Aphasia• Cause: early focal lesion• Language delayed• Lesion location:

• not predictive of type !• articulation: OK

Prognosis: • ~ good• reading ± OK• often ↓ visual/spatial skills

• CT/MRI: informative

Developmental• Cause: ~ genetic • Language delayed• Several subtypes:

• most receptive/expressive, • others expressive, fluent

Prognosis: • variable• reading ~ impaired• often: + other dev. disorder

• CT/MRI: ~ useless

Acquired aphasia in toddlers/older children

Parallel the aphasia syndromes of adults

Recovery of language tends to be better than in adults but is by no means necessarily complete

Sequelae: depend on size/location of lesion

Sequelae: almost invariably reading/ academic problems ± cognitive deficits

Cortical Calculation Networks

Dehaene, 2001

Calculation: Relevant Cortical Circuitry

Occipito-parietal (dorsal, “where”) visual stream intraparietal sulcus L > R

Occipito-temporal (ventral, “what”) visual stream fusiform gyrus

Lateral prefrontal cortex♦ Working memory

♦ Attention

♦ Executive skills

Dyscalculia

Difficulty acquiring basic arithmetic skills Detected later than dyslexia Requirements: adequate

♦ language skills♦ visuo-spatial skills♦ memory, working (& long-term)♦ executive skills, including attention

Children with dyscalculia Control children

Kucian et al. 2006

Gerstmann syndrome (1920s)

In acquired Lt ~ angular gyrus lesion♦ R-L confusion♦ Finger agnosia♦ Dyscalculia♦ Dysgraphia

Developmental Gerstmann syndrome (Kinsbourne & Warrington 1963)

♦ All of the above♦ Constructional dyspraxia

Stevenson et al., Science 1986

Roots of American lower SEM than Asians: School hours/week on

language vs. math

Japan Taiwan U.S.

INTERVENTION

Effect of Practice on the Brain

Violinists: ↑ cortical finger representation

Musicians vs non-musicians: altered hemispheric dominance for music

Wine tasters: much enhanced smell discrimintion

Dancers, athletes: enhanced cerebellar activation

Remediation

Training / education is the most powerful tool we have to alter / improve brain structure and function

But… brain plasticity is limited by♦ severity of pathology♦ location of pathology♦ age at time of insult♦ adequacy of the intervention!

Cochlear Implant

Requirement: viable neurons in spiral ganglion

Early in prelingual deafness: activates the central

auditory pathway → quite effective

Late in prelingual deafness: activates primary but

not secondary auditory cortex → more limited

effectiveness

In previously hearing person → effective

In all cases: requires intensive and prolonged

training